A Phase II-R and a Phase III Trial Evaluating Both Erlotinib (Ph II-R) and Chemoradiation (Ph III) as Adjuvant Treatment for Patients With Resected Head of Pancreas Adenocarcinoma

简要总结

详细描述

PRIMARY OBJECTIVES: I. To determine whether the addition of erlotinib (erlotinib hydrochloride) to gemcitabine (gemcitabine hydrochloride) adjuvant chemotherapy shows a signal for improved survival as compared to gemcitabine alone following R0 or R1 resection of head of pancreas adenocarcinoma (including adenocarcinoma of the head, neck, and uncinate process). (Phase II-R) II. To determine whether the use of concurrent fluoropyrimidine and radiotherapy following adjuvant gemcitabine based chemotherapy or non-gemcitabine based chemotherapy such as modified fluorouracil-leucovorin-irinotecan-oxaliplatin regimen (FOLFIRINOX) further enhances survival for such patients who are without evidence of progressive disease after 5 months of adjuvant chemotherapy. (Phase III) SECONDARY OBJECTIVES: I. To evaluate disease-free survival of adjuvant chemotherapy followed by radiotherapy and concurrent fluoropyrimidine for patients with resected head of pancreas adenocarcinoma who are disease free after 5 months of adjuvant chemotherapy. II. To evaluate disease-free survival of standard adjuvant gemcitabine chemotherapy with and without erlotinib for patients with resected head of pancreas adenocarcinoma. III. To evaluate adverse events with and without erlotinib for patients with resected head of pancreas adenocarcinoma. IV. To evaluate adverse events of adjuvant chemotherapy with or without radiation therapy and concurrent fluoropyrimidine for patients with resected head of pancreas adenocarcinoma who are disease free after adjuvant chemotherapy. V. To evaluate preoperative cross-sectional imaging of the primary head of pancreas adenocarcinoma in order to determine the frequency with which objective criteria of resectability are present. VI. To determine if patients reporting low baseline fatigue, as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, predicts survival and to explore correlations between baseline fatigue, as measured by Patient-Reported Outcomes Measurement Information System (PROMIS), and survival. OUTLINE: Patients without disease progression after treatment in arm I or II are randomized to 1 of 2 additional treatment arms (arm III or IV). ARM I: Patients receive either gemcitabine hydrochloride or allowable combination chemotherapy per standard of care for 5 months. ARM II (closed to accrual 4/2/14): Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes once a week for 3 weeks then off 1 week and erlotinib hydrochloride orally (PO) once daily on days 1-28. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. ARM III: Patients receive the same treatment as in arm I for 1 month. ARM IV: Patients receive the same treatment as in arm I for 1 month. Beginning within 7-21 days after completion of chemotherapy, patients undergo radiotherapy (3-dimensional conformal radiotherapy or intensity-modulated radiotherapy) 5 days per week for 5.5 weeks (28 fractions). During radiotherapy, patients receive either capecitabine PO twice daily (BID) 5 days per week or fluorouracil IV continuously for 5.5 weeks or until radiotherapy is completed. Patients undergo computed tomography (CT), magnetic resonance imaging (MRI), and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline. After completion of study treatment, patients are followed up every 3-6 months for up to 4 years, then yearly.

主要结局

次要结局

• Disease-free Survival (Percentage of Participants Alive Without Disease) [Phase III](From step 2 randomization (chemotherapy vs. chemotherapy followed by chemoradiation) to disease event, death, or last follow-up. Maximum follow-up at time of the phase III analysis was 12.8 years, measured from step 2 randomization.)
• Number of Participants by Highest Grade Adverse Event Reported (Phase II)(From step 1 randomization (gemcitabine vs. gemcitabine/erlotinib) to death or last follow-up. Maximum follow-up at the time of the phase II analysis was 6.2 years.)
• Number of Participants by Highest Grade Adverse Event Reported (Phase III)(From step 2 randomization (chemotherapy vs. chemotherapy followed by chemoradiation) to death or last follow-up. Maximum follow-up at time of the phase III analysis was 12.8 years, measured from step 2 randomization.)
• Disease-free Survival (Percentage of Participants Alive Without Disease) [Phase II](From step1 randomization (gemcitabine vs. gemcitabine/erlotinib) to disease event, death, or last follow-up. Maximum follow-up at the time of the phase II analysis was 6.2 years. Five-year rates are reported here.)
• Overall Survival (Percentage of Participants Alive) by Baseline Fatigue Group(From enrollment (step 1) to death or last follow-up. Maximum follow-up at time of the phase III analysis was 13.2 years, measured from enrollment. Two- and five-year rates are reported here.)